Connectivity theory of Autism: Using connectivity measures in the assessment and treatment of autistic disorders

Transcription

1 Connectivity theory of Autism: Using connectivity measures in the assessment and treatment of autistic disorders Presented at Advances in Cerebral Connectivity Monterey, California Robert Coben,PhD

2 Neuroimaging findings in Autism MRI decreased grey matter volume, frontostriatal, parietal networks. White matter reductions in cerebellum, internal capsule, fornices (McAlonan et al, 2004) PET bilateral temporal hypoperfusion, superior temporal gyrus/sulcus (Boddaert et al., 2002) Social cognitive and language dysfunctions have been linked to neural substrates amygdala, superior temporal sulcus, fusiform gyrus (Just et al., 2004; Pelphrey et al., 2004; Welchew et al, 2005)

3 Connectivity in Autistic disorders MRI reductions in white matter (McAlonan et al., 2004) fmri underconnnectivity in anterior-posterior connections (Cherkassky et al., 2006) fmri hyperconnectivity across middle frontal regions (Mizuno et al., 2006). Theory of hyperconnected frontal cortices along with frontal to other hypoconnectivity (Courchesne & Pierce, 2005).

4 Connectivity findings in Autism Less white matter concentration in the genu, rostrum, splenium (Chung et al., 2004) Cell columns are more numerous, smaller and less compact in frontal and temporal regions (Casanova et al, 2002) Diminished connectivity in language areas during sentence comprehension (Just et al., 2004) 124 channel EEG higher than nornal neural connectivity and lower than normal connectivity between frontal and other brain regions (Murias, 2006)

5 fmri coherence in Autism

6 White matter anomalies in Autism

7 Connectivity theory of Autism Neural development and connectivity is stunted at an early developmental stage when the frontotemporal regions are undifferentiated. This lack of differentiation or independent development of brain regions leads to their hyperconnectivity and blocks coherence development with other critical brain regions. What is unknown is why this occurs, what can prevent it and what can be done about it. We are learning that NF can significantly alter this patterns in a more functional direction.

8 Classification Accuracy Coben, Chabot, Hirshberg (2007): ASD vs. Normals vs. ADHD (N = 68, 250+) Ages 5 18, matched for age and sex ASD (90.1%) (88.7% replication) vs Normals (93.9%) (93% replication) ASD (84.5%) (81.7% replication) vs. ADHD (84.3%) (83.6% replication)

9 Discriminant function critical variables Increased theta relative power Increased frontal/temporal beta coherence (ADHD) Decreased temporal coherence Central/Parietal decreased coherence (normals)

10 Coben, Hudspeth, Clarke & Barry (2006). EEG in autistic disorders: Power and connectivity analyses. Coben, Clarke, Barry & Hudspeth (2006) 27 Autistics and 27 Normals matched for age, race, gender, medication usage (none). Normals had mean IQ =103.2, mean age = 9 years, 8 months, screened for reading, spelling, behavior problems, head injury, ADHD, medication use, psychiatric diagnosis, learning problems. QEEG performed resting eyes closed. All EEG artifacting done by same person with over 30 years experience.

11 Coben, Hudspeth, Clarke & Barry (2006). EEG in autistic disorders: Power and connectivity analyses.

12 Mu rhythm and suppression in Autism: The Mirror Neuron System

13 Mu rhythm oscillations

14 The importance of Mu/MNS

15 Coben & Hudspeth (2007). Mu osciallations in autistic disorders and their underlying mechanisms. Example of Mu-like Rhythm Oscillations

16 Coben & Hudspeth (2007). Mu osciallations in autistic disorders and their underlying mechanisms. Part 1: EEG Analyses Sampled 56 QEEG profiles diagnosed with ASD and not taking any medications. Selected for mu-like rhythm oscillations over C3, C4. Activity did not diminish upon eye opening (lack of mu suppression) yes no

17 Coben & Hudspeth (2007). Mu osciallations in autistic disorders and their underlying mechanisms. Part 1: EEG Analyses C3, C hz. Maximal 8 13 hz. Range Spectral Sort Median splits C3: p<.015 C4: p<.021 Sorted into high and low mu-like records

18 Coben & Hudspeth (2007). Mu osciallations in autistic disorders and their underlying mechanisms.

19 Patterns of EEG Connectivity anomalies in Autistic disorders 1. Frontotemporal hyperconnectivity 2. Frontal (orbitofrontal) hypoconnectivity 3. Mu rhythm complex mixed sensorimotor hypoconnectivity with frontal hyperconnectivity 4. Right posterior (occipital/parietal- temporal) hypoconnectivity 5. Frontal posterior hypoconnectivity 6. Left hemisphere intrahemispheric hypoconnectivity 7. Left hemisphere intrahemispheric hyperconnectivity

20 Frontotemporal hyperconnectivity

21 Frontotemporal hyperconnectivity

22 Frontotemporal hyperconnectivity Coben & Padolsky (2006). Assessment Guided Neurofeedback for ASD. 37 Autistics seen in our practice for at least 20 sessions of EEG Biofeedback. During this time frame, only one patient dropped out. Compared to 12 WLC. Parental Judgment. Pre and Post ATEC, GADS, BRIEF, PIC-2. Pre and Post Neuropsychological testing and QEEG. Pre and Post Infrared Imaging surrounding each session.

23 Frontotemporal hyperconnectivity Autistic Diagnoses Autism PDD Aspergers CDD

24 Frontotemporal hyperconnectivity Neurofeedback Protocols 89% Interhemishperic, bipolar. 94% Frontotemporal electrode sites. 100% high beta inhibit (18-30 hz). 92% has low inhibits down to 1-2 hz. 68% had a third inhibit in the 7-14 hz region Reward bands setup for maximal hyperconnectivity 5-16 hz.

25 Frontotemporal hyperconnectivity Results: Parental Judgment Benefit:Harm Ratio = 89

26 Frontotemporal hyperconnectivity Results: Parent Ratings 40% reduction in symptoms

27 Frontotemporal hyperconnectivity

28 Frontal (orbitofrontal) hypoconnectivity

29 Frontal (orbitofrontal) hypoconnectivity

30 Frontal (orbitofrontal) hypoconnectivity

31 Frontal (orbitofrontal) hypoconnectivity Coben (2006). HEG for ASD. 28 Autistics seen in our practice for at least 20 sessions of HEG (nir or pirheg). All patients had already received 20 sessions of EEG Biofeedback. This was assessment guided HEG in that all patients were deemed to have frontal system dysfunction based on NP, IR and QEEG data. Pre and Post ATEC, GADS, BRIEF, PIC-2. Pre and Post NP testing. Pre and Post Infrared Imaging surrounding each session. Pre and Post QEEG.

32 Frontal (orbitofrontal) hypoconnectivity HEG Procedures nirheg or pirheg therapy remained the same over the entire course of 20 sessions. Sessions were minutes depending on tolerance. Done twice weekly. Therapy was done with DVD and/or Gamecube video games.

33 Frontal (orbitofrontal) hypoconnectivity Control Sample 12 subjects in wait list control group. Matched for gender, age, race, handedness, other treatments, initial ATEC score. No new treatment during study design. Pre-post testing showed no significant changes on any measure.

34 Frontal (orbitofrontal) hypoconnectivity Results: ATEC ratings Total p< % reduction Communication p< % reduction Socialization p< % reduction Sensory/Cognition p< % reduction Behavior p< % reduction

35 Frontal (orbitofrontal) hypoconnectivity nirheg/pirheg Comparisons nir pir pragmatics emotional control social skills IR 1st range No significant difference for ATEC scores, GADS ADQ, BRIEF Working Memory, PIC-2 ADH, Deliquency, Family relations, Psychological discomfort, or any Neuropsychological index.

36 Frontal (orbitofrontal) hypoconnectivity nirheg/pirheg Comparisons Relative Power pirheg nirheg

37

38 Mu rhythm complex

39 Mu rhythm complex

40 Mu rhythm complex

41 Mu rhythm complex Part 2: Neurofeedback Outcome Study 14 patients underwent 20 sessions EEGBF. Pre-post NP tests, NB rating scales, IR imaging, QEEG. Two comparison groups: Coherence training Interhemispheric, bipolar training

42 Mu rhythm complex Part 2: Neurofeedback Outcome Study Total NF group (14 patients) had significant changes in : GADS Pragmatics p<.006 GADS Social Interaction p<.027 GADS ADQ p<.014 Executive Functioning p<.0001 Visuospatial Skills p<.004 Attention p<.005 IR enduring change min value p<.033 IR enduring change range p<.05

43 Mu rhythm complex Part 2: Neurofeedback Outcome Study: Comparative Analyses coherence 3 bipolar pragmatics attention (sd) 0.37 IR min Total M u Change (x10)

44 Mu rhythm complex Part 2: Neurofeedback Outcome Study: Comparative Analyses: QEEG changes Bipolar Coherence

45 Mu rhythm complex

46 Mu rhythm complex

47 Mu rhythm complex

48 Mu rhythm complex

49 Right posterior (occipital/parietal temporal) hypoconnectivity

50 Right posterior (occipital/parietal temporal) hypoconnectivity

51 Right posterior (occipital/parietal temporal) hypoconnectivity

52 Frontal posterior hypoconnectivity

53 Frontal posterior hypoconnectivity

54 Left hemisphere hypoconnectivity

55 Left hemsiphere intrahemispheric hyperconnectivity